The binding of transcription factor proteins to the promoter DNA is a crucial step in the control of gene expression. Gene expression is activated (or repressed) when the activation (or repression) domain of the transcription factor is tethered to the promoter through its DNA-binding domain. The main goal of Phase I of this project is to devise novel means for bringing the activation or repression domains to the promoter. Instead of using the DNA-binding domain, we will apply a novel methodology to accomplish the same effect. The crucial advantage of this method lies in the ability to expand the range of molecules that could be tested in transcriptional assays. This includes completely artificial, non-peptidic compounds. The long-term goal of this project is to develop new experimental strategies for screening the chemical combinatorial libraries for compounds that are active in transcriptional assays. Such molecules will have a significant pharmacological potential and will lead to a new class of drugs that target genes at the level of transcription. PROPOSED COMMERCIAL APPLICATION: Not available.